West and West-like Syndrome Most Common Severe Epilepsy Syndromes at Infancy

Katherine Howell, MD

A recent study investigated incidence and etiologies of severe epilepsies of infancy (SEI) and found that 3 quarters of SEIs could be assigned an epilepsy syndrome or “variant syndrome” at presentation.

West syndrome (WS) and “WS-like” syndrome had a combined incidence of 32.7 out of 100,000 live births per year (95% CI, 26-41). The incidence of SEI with migrating focal seizures (EIMFS) was 4.5 out of 100,000 (95% CI, 2.4-8.4) and the incidence of infantile epileptic encephalopathy (EIEE) was 3.6 out of 100,000 (95% CI, 1.8-7.2). All cases of “WS-like” epilepsy, 83% of unifocal epilepsy cases and 39% of WS cases had structural etiologies. EIMFS, EIEE, and Dravet syndrome (DS) mainly consisted of single gene disorders. 

First author Katherine Howell, MD, clinician-scientist fellow and epilepsy team leader, Murdoch Children's Research Institute, and pediatric neurologist and epileptologist, Royal Children's Hospital and colleagues wrote that “diagnosis of an epilepsy syndrome, with allowance for minor variations, is feasible in most infants and remains clinically useful, potentially helping to guide investigation and prognostication, given important differences in etiology and outcome between syndromes.”

Howell and colleagues investigated 114 infants from Victoria, Australia with SEIs with a median age of seizure onset of 4.6 months (interquartile range [IQR], 5.4), 61 (51%) of which were male. Of these infants, 73 (64%) of which fulfilled diagnostic criteria for epilepsy syndromes and 16 (14%) had “variants” of epilepsy syndromes in which one feature was different or missing, or not all classical features had emerged yet. 

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The most common syndromes were WS (n = 41; 36%) and WS-like (n = 11; 10%) epilepsies. Unifocal epilepsy was present in 12 (11%) infants, EIMFS in 10 (9%), EIEE in 8 (7%), and early myoclonic encephalopathy (EME) in 2 (2%). EME was found to have an incidence of 0.9 out of 100,000 live births per year (95% CI, 0.23-3.6). By 2 years of age, the epilepsy syndrome had evolved to a different syndrome in 45 (39%) infants. The most common evolution was to WS or WS-like syndromes in 25 (22%) infants. 

Howell and colleagues identified underlying etiology in 85 (75%) infants. A malformative structural etiology was present in 32 (28%) while an acquired structural etiology was present in 14 (12%). Single gene disorders were identified in 23 (20%) infants, chromosomal disorders in 9 (8%), and metabolic conditions in 7 (6%). A genetic basis was identified in 46% of infants, out of 100 with nonacquired etiologies.

Investigating outcomes revealed that 18 (16%) infants died before age 2. Half the infants with EIEE (4 of 8), EME (1 of 2) and 60% with EIMFS (6 of 10) died. WS and WS-like epilepsy had the lowest mortality rates compared to other syndromes (1 of 52; P <.01). 

At age 2, 46 (48%) infants had ongoing seizures and were on antiseizure medications (ASMs). Fifty had controlled seizures, 25 of which were on ASMs. Out of infants with EIEE, EME, EIMFS, or possible DS, 21 of 24 (88%) had ongoing seizures until death or 2 years of age.

Borderline or delayed development was present in 85 of 96 (89%) survivors, with a severe-profound impact in development seen in 40 (42%). Development was normal in 11 (11%) infants. Out of infants with EIEE or EIMFS, all had severe-profound delayed development or were deceased, while 19 of 64 (30%) infants with WS, WS-like, or unifocal epilepsy had severe-profound delays and 2 (3%) were deceased.

“An epilepsy syndrome diagnosis is still important even in the setting of a known etiology, as many epilepsy genes are associated with a spectrum of epilepsy syndromes that require different interventions. This can include genes that can cause both milder and severe epilepsies, such as the spectrum of SCN1A pathogenic variants, which ranges from DS to febrile seizures. Even within the severe epilepsies due to a single gene, different epilepsy syndromes may show the opposite response to an ASM, such as sodium channel blockers in SCN2A, reflecting the underlying mechanism,” Howell and colleagues wrote.

“Understanding both epilepsy syndrome and etiology is thus essential as knowledge of individual etiologies increases and novel etiology-specific and syndrome-specific treatments become available,” they concluded.

REFERENCE

Howell KB, Freeman JL, MacKay MT, et al. The severe epilepsy syndromes of infancy: A population‐based study. Epilepsia. Published online January 21, 2021. doi: 10.1111/epi.16810